HS-20089 in Patients With Ovarian Cancer and Endometrial Cancer

Prior treatment

• Presence of Grade ≥ 2 toxicities as per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) due to prior anti-tumor therapy (except alopecia and residual neurotoxicity).
• Evidence of brain metastasis, unless meeting all of the following criteria:
  • Asymptomatic; medically stable for at least four weeks prior to the first dose;
  • No steroid treatment required for at least two weeks prior to the first dose;
  • No stereotactic radiation therapy, whole brain radiotherapy, and/or neurosurgical resection within 4 weeks prior to the first dose;
  • No history of intracranial or spinal hemorrhage;
  • Have at least one target lesion other than CNS lesion according to RECIST v1.1;
• Clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose of study treatment.
• Serious arteriovenous thromboembolic events within 3 months prior to the first dose of study treatment.
• Serious infections within 4 weeks prior to the first dose.
• Have received systemic glucocorticoid therapy for more than 30 days within 30 days prior to the first dose study treatment, or require chronic (≥ 30 days) use of systemic glucocorticoids during the study, or have other acquired, congenital immunodeficiency disorders, or a history of organ transplantation.
• Attenuated live vaccination within 4 weeks prior to the first dose.
• Allergies or hypersensitivity reactions within 4 weeks prior to the first dose. History of severe allergies (e.g., anaphylactic shock), or severe infusion-related reactions. Allergy or hypersensitivity to any component of HS-20089.

Other illness

• Known history of prior malignancy.
• Severe, uncontrolled or active cardiovascular disorders.
• Serious or poorly controlled diabetes.
• Serious or poorly controlled hypertension.
• Presence of active infectious diseases such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus infection, etc.
• Current hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B or more severe cirrhosis.
• Any moderate or severe lung diseases that may interfere with the detection and treatment of drug-related pulmonary toxicity or may seriously affect respiratory function.
• History of severe neurological or psychiatric disorder.
• Subjects with any condition that jeopardizes the safety of the patient or interferes with the assessment of the study, as judged by the investigator.

Lab values

• Have received or is currently receiving the following treatment:
  • B7-H4-targeted therapies.
  • Have received any of cytotoxic chemotherapy drugs, investigational drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs (including endocrine therapy, molecular targeted therapy, biotherapy, etc.) within 14 days prior to the first dose of study drug; or need to continue these drugs during the study.
  • Have received macromolecular antitumor drugs (including immunotherapy, such as monoclonal antibodies and bispecific antibodies) within 28 days prior to the first dose of study drug.
  • Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.
  • Major surgery (such as craniotomy, thoracotomy or laparotomy, etc.) within 4 weeks prior to the first dose of study treatment.
  • Use of strong inhibitors or inducers of CYP3A4, CYP2D6, P-gp, or BCRP, or sensitive substrates of CYP3A4, CYP2D6, P-gp, or BCRP with narrow therapeutic window within 7 days prior to the first dose of study drug; or in need of continuing treatment with these drugs during the study.
  • Current use of drugs known to prolong the QT interval or potentially cause torsades de pointes; or need to continue these medications during the study.

Other

• Presence of pleural/abdominal effusion requiring clinical intervention.
• Inadequate bone marrow reserve or hepatic/renal functions.
• Cardiological examination abnormality.
• Pregnant or breast-feeding women or women who intend to become pregnant during the study.
• Subjects unlikely to comply with study procedures, restrictions and requirement as determined by the investigator.

• Males or females aged 18 years or older (≥18 years).
• Patients diagnosed with recurrent or metastatic ovarian cancer, endometrial cancer or other solid tumors.
• Subjects have at least one target lesion as assessed per the RECIST 1.1. Patients with only brain and/or bone lesions as target lesions are ineligible.
• Tumor tissue from a newly obtained biopsy (FFPE tumor tissue blocks or slides are acceptable) is required. If the newly obtained biopsy is not feasible, newly obtained FFPE slides cut from archival tumor tissue blocks within 2 years prior to the first dose of study drug are acceptable.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 1 and no deterioration within 2 weeks before the first dose.
• Have a life expectancy of at least 12 weeks.
• Female subjects of childbearing potential are willing to take appropriate contraceptive measures and should not breastfeed from signing the informed consent until 6 months after the last dose; male subjects must agree to use barrier contraception (i.e. condoms) from signing the informed consent to 6 months after the last dose.
• Female subjects must have a negative pregnancy test within 7 days prior to the first dose (for subjects with tumor related abnormal elevation of human chorionic gonadotropin \[HCG\], an ultrasound of uterus and appendages should be performed within 7 days prior to the first dose to rule out pregnancy), or demonstrate no risk for pregnancy.
• Subject must be voluntarily enrolled in this clinical trial, be able to understand the study procedures and to sign written informed consent.